title: Marked liver tumorigenesis by Helicobacter hepaticus requires perinatal exposure.
abstract: BACKGROUND
  Although severe hepatitis and liver tumors occur in a high percentage of A/J male mice naturally infected with Helicobacter hepaticus, these effects have not been observed after injection of adult mice with the bacteria.
  
  
  OBJECTIVE
  We tested the hypothesis that perinatal exposure to the bacteria is required for liver tumorigenesis.
  
  
  METHODS
  A/J female mice were infected by intragastric (ig) or intraperitoneal (ip) treatment with 1.5 x 10(8) H. hepaticus before pregnancy. We examined offspring at progressive time intervals, including some kept until natural death in old age. A/J, BALB/c, and C57BL/6 weanling male mice were similarly treated ig with the bacteria and observed for up to 2 years.
  
  
  RESULTS
  After ip bacterial infection of A/J females, 41% of their male offspring developed hepatitis and 33% had hepatocellular tumors, including 18% with hepatocellular carcinoma. Treatment by the ig route resulted in a similar incidence of hepatitis in offspring (35%) but fewer total liver tumors (8%) and carcinomas (4%). By contrast, ig instillation of H. hepaticus in weanling A/J, C57BL/6, or BALB/c mice resulted in low incidence of hepatitis (0-20%) and few liver tumors, despite presence of bacteria confirmed in feces.
  
  
  CONCLUSIONS
  Results indicate that a high incidence of liver tumors in mice infected with H. hepaticus requires perinatal exposure. Contributing perinatal factors could include known high sensitivity of neonatal liver to tumor initiation, and/or modulation of immune response to the bacterium or its toxins. Mechanisms of human perinatal sensitivity to such phenomena can be studied with this model.
authors.affiliation: Basic Research Program, SAIC-Frederick, Inc., Frederick, Maryland, USA.
authors.forename: Bhalchandra A
authors.initials: BA
authors.lastname: Diwan
authors.forename: Marek
authors.initials: M
authors.lastname: Sipowicz
authors.forename: Daniel
authors.initials: D
authors.lastname: Logsdon
authors.forename: Peter
authors.initials: P
authors.lastname: Gorelick
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Anver
authors.forename: Kazimierz S
authors.initials: KS
authors.lastname: Kasprzak
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Anderson
mesh_terms: D000818:Animals; D005260:Female; D044923:Helicobacter hepaticus / Q000472:pathogenicity*; D008114:Liver Neoplasms, Experimental / Q000382:microbiology*; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D013045:Species Specificity